The major emphasis of the proposed research is the investigation of several types of tumor viruses as model systems to study the molecular mechanisms of transformation. The areas of investigation are as follows: A. Herpes Viruses: 1. Studies to identify the genes of herpes simplex virus which are required for transformation. 2. Studies to investigate possible relationships between herpes simplex virus and Epstein-Barr virus. 3. Studies of the mechanism of transformation of human lymphocytes by Epstein-Barr virus. B. Papova Viruses: Isolation and characterization of promoter mutants of SV40 to study regulation of early gene expression. C. RNA Tumor Viruses: 1. Studies of endogenous viral genomes in uninfected cells. 2. Investigation of genetic interactions between exogenous viruses and their host cells.